The overall goal of this UOI application is to create and support a highly multidisciplinary team of chemists, biologists, engineers and physicians to develop and rapidly translate new nanotechnologies to better diagnose and treat heart, lung, blood and sleep (HLBS) disorders. The current team includes investigators from the newly formed Broad Institute, Massachusetts Institute of Technology (MIT), Harvard Faculty of Arts and Sciences (FAS), Harvard Medical School (HMS), Massachusetts General Hospital (MGH) and Brigham and Women's Hospital (BWH). Specific applications of nanotechnology in this application include noninvasive imaging and sensing, targeted therapies, tissue repair and regeneration and drug delivery. The team's aims are to: 1. (Stellacci, Josephson) investigate novel metal and semiconductor nanoparticles for improved in vivo sensing and targeting. 2. (Shaw, Perez, Weissleder, Schreiber) create and test entire libraries of nanoparticles as a proof-of-principle to rapidly engineer nanomaterials with precise biological function. 3. (Shaw, Schreiber) develop multidimensional cell screens to rapidly and sensitively test biosafety of novel materials. 4. (Lee, Zhang, Anversa) harness smart scaffolds capable of growth factor release to promote cardiovascular tissue regeneration ("liquid heart"). 5. (Libby, Weissleder, Swager) utilize novel polymeric composites to sense reactive oxygen species in vulnerable plaque. 6. (Shapiro, Tung) utilize novel protease sensors for early in vivo sensing of smoke induced lung injury. 7. (Jaffer, Reed, Wagner) test novel targeted and activatable fibrinolytic scaffolds for enhanced therapies of thrombotic events. It is anticipated that these advances in nanotechnology will significantly advance medical science and treatment of HLBS disorders.